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. 2021 Jun 3;8(16):2101090. doi: 10.1002/advs.202101090

Figure 5.

Figure 5

Targeting inflammation to restore or penetrate the BBB. Targeting inflammation and downstream sequalae, including angiogenesis, oxidative stress, or cytoskeleton reorganization, restores the BBB. Pharmacological inhibitors of inflammatory cytokines rescue damage to the BBB. Inhibitors of angiogenesis (e.g., antibodies targeting VEGF/VEGFR) and oxidative stress (inhibitor to NOXs) restore BBB integrity. Targeting immune cells is an alternative way to inhibit inflammation. Natalizumab, which targets the α4 integrin (ITGA4), prevents the recruitment of immune cells to brain endothelial cells by inhibiting the integrin‐VCAM1 interaction and greatly rescues BBB integrity. IFN‐α/β enhances BBB integrity via activation of Rac‐1. IFN‐λ tightens the BBB through restricting IFNLR1 in the BBB. Cytoskeleton reorganization is downstream effect of inflammation and disrupts the BBB through actin polymerization. Fasudil (ROCK inhibitor), Heat shock protein 27 (HSP27), LY‐317615 (PKCβ inhibitor) all restore the BBB by re‐normalizing the cytoskeleton.